Stability of three cephalosporin antibiotics in AutoDose Infusion System bags

OBJECTIVE: To evaluate the physical and chemical stability of three commonly used cephalosporin antibiotic solutions packaged in AutoDose Infusion System bags stored and evaluated at appropriate intervals for up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to the AutoDose Infusion System bags and diluting to the target concentration with 0.9% sodium chloride injection. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods of up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. RESULTS: All of the cephalosporin admixtures were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples turned a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis showed that cefazolin sodium and ceftriaxone sodium remained stable for 30 days and ceftazidime remained stable for 7 days at 4 degrees C. At room temperature, losses were much more rapid. Cefazolin sodium and ceftriaxone sodium retained at least 90% of their initial concentrations through 7 days and 5 days, respectively, when stored at 23 degrees C. Ceftazidime remained stable for only 1 day at 23 degrees C. CONCLUSION: Cefazolin sodium, ceftazidime, and ceftriaxone sodium exhibited physical and chemical stabilities consistent with those found in previous studies of these drugs. The AutoDose Infusion System bags did not adversely affect the physical and chemical stabilities of these three cephalosporin antibiotics.     

Compatibility and stability of linezolid injection admixed with aztreonam or piperacillin sodium

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with aztreonam (Azactam-Squibb) 2 grams and separately with piperacillin sodium (Pipracil-Lederle) 3 grams over 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test samples were prepared by adding the required amount of aztreonam or piperacillin sodium to separate bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical compatibility and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C. RESULTS: All of the linezolid admixtures with aztreonam and with piperacillin sodium were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change throughout the study at both storage temperatures. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Aztreonam in the linezolid admixtures was stable for 7 days, exhibiting less than 5% loss at 4 degrees C and 9% loss at 23 degrees C. Piperacillin sodium in the linezolid admixtures was stable for 7 days at 4 degrees C, exhibiting no loss, but was stable for only 3 days at 23 degrees C with losses of about 5%. Losses had increased to 9% to 12% after 5 days of storage at room temperature. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with aztreonam 2 grams or piperacillin sodium 3 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C and for 7 days or 3 days, respectively, at 23 degrees C.     

Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions

In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.     

Stability of intravenous admixtures containing aztreonam and cefazolin

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.     

Stability of intravenous admixtures of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin

The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.     

Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures.     

Stability of methylprednisolone sodium succinate in autodose infusion system bags

OBJECTIVE: To evaluate the physical and chemical stabilities of methylprednisolone sodium succinate solutions packaged in sterile AutoDose Infusion System bags. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by reconstituting the methylprednisolone sodium succinate, adding the required amount of drug to the AutoDose Infusion System bags, and diluting to the target concentrations of 100 mg/100 mL and 1 gram/100 mL with 0.9% Sodium Chloride Injection. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods up to 3 days at 23 degrees C and 30 days at 4 degrees C. RESULTS: The admixtures initially were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change. All samples were essentially colorless throughout the study. High-performance liquid chromatography analysis revealed some decomposition in the samples. Methylprednisolone sodium succinate exhibited about 8% loss after 2 days and about 13% loss after 3 days at 23 degrees C. In the samples stored at 4 degrees C, methylprednisolone sodium succinate exhibited acceptable stability through 21 days of storage, but losses exceeded 10% after 30 days. CONCLUSION: Methylprednisolone sodium succinate exhibited physical and chemical stabilities consistent with those found in previous studies. The AutoDose Infusion System bags did not adversely affect the physical or chemical stability of this drug.     

Stability of intravenous admixtures of doxorubicin and vincristine

The stability of doxorubicin and vincristine in admixtures containing both drugs in 0.9% sodium chloride injection, 0.45% sodium chloride and Ringer's acetate injection, and 0.45% sodium chloride and 2.5% dextrose injection was studied. Doxorubicin hydrochloride was added to 30-mL quantities of each base solution to achieve initial doxorubicin concentrations of 1.40 mg/mL and to 0.9% sodium chloride injection to achieve concentrations of 1.88 and 2.37 mg/mL. Vincristine sulfate was added to each doxorubicin admixture to achieve vincristine concentrations of 0.033 and 0.053 mg/mL. All admixtures were protected from light and stored in polysiloxan bags that are used with portable delivery devices. Admixtures were kept at temperatures of 25, 30, and 37 degrees C. Samples withdrawn immediately after preparation and at 1, 2, 4, 7, 10, and 14 days were analyzed by high-performance liquid chromatography for content of each drug. The stability of doxorubicin was dependent on temperature and composition of the base solution. Analysis of data from the samples containing 0.45% sodium chloride and Ringer's acetate injection showed that doxorubicin concentrations were less than 90% of the initial concentration by 12 hours at 37 degrees C, 35 hours at 30 degrees C, and 62 hours at 25 degrees C, and visual changes occurred in all of these admixtures over the course of the study. Vincristine degradation also was most rapid in 0.45% sodium chloride and Ringer's acetate admixtures. Data analysis showed that concentrations of vincristine were less than 90% of initial after eight days at 25 degrees C, five days at 30 degrees C, and three days at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of floxuridine and leucovorin calcium admixtures for intraperitoneal administration

The stability of floxuridine and leucovorin calcium in admixtures of 0.9% sodium chloride injection at various concentrations, temperature conditions, and time points was determined. Admixtures of floxuridine and leucovorin calcium were prepared in 1-L plastic bags containing 0.9% sodium chloride injection. Admixtures containing the following three concentrations were prepared: floxuridine 1 g and leucovorin calcium 30 mg, floxuridine 2 g and leucovorin calcium 240 mg, and floxuridine 4 g and leucovorin calcium 960 mg. The admixtures were stored at refrigerated temperature (4-8 degrees C), ambient room temperature (20 degrees C), and near-physiologic body temperature (40 degrees C). Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) method at 0, 4, 8, 24, and 48 hours (4-8 degrees C) and at 0, 1, 3, 6, 24, and 48 hours (20 degrees C and 40 degrees C). A second set of samples at the same concentrations was prepared and sequentially stored at refrigerated, room, and near-physiologic temperatures to simulate actual-use conditions; these samples were assayed by HPLC at 0, 4, 8, 24, and 48 hours (4-8 degrees C); 49, 51, 54, and 60 hours (20 degrees C); and 61, 63, 66, and 72 hours (40 degrees C). All solutions were protected from light. Floxuridine and leucovorin calcium were stable at each concentration and temperature condition tested for a minimum of 48 hours. However, leucovorin calcium was more subject to decomposition at near-physiologic temperature than at other temperatures, with the most degradation at the lowest concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of mitomycin admixtures

The stability of mitomycin in admixtures for continuous intravenous infusion was studied. Mitomycin was reconstituted and diluted to 50 micrograms/mL in polyvinyl chloride minibags containing 5% dextrose injection 50 mL or 0.9% sodium chloride injection 50 mL. Additional mitomycin admixtures were reconstituted with a buffer solution containing monobasic and dibasic sodium phosphate; these were diluted with 5% dextrose injection only. Admixtures were stored at room temperature (27-30 degrees C) and refrigerated temperature (5 degrees C) for 120 days. Mitomycin concentrations in each admixture were tested by high-performance liquid chromatography (HPLC) immediately after admixture and at intervals during storage. Ultraviolet spectra were determined at the same time as HPLC analysis, and the admixtures were visually inspected and tested for pH. Mitomycin concentrations decreased rapidly in the unbuffered admixtures; after 12 hours at room temperature, less than 26% of the drug remained in the dextrose admixture. When the unbuffered admixtures were refrigerated for 12 hours, the mitomycin concentrations decreased 10% in the sodium chloride admixtures and 33% in the dextrose admixtures; after 24 hours, the percentages of drug loss were 23% and 42%, respectively. Mitomycin concentrations in the buffered admixtures showed no substantial decrease during 120 days at 5 degrees C. At room temperature, concentrations decreased 10% after 15 days. When the admixture is buffered to a pH of approximately 7.8, mitomycin is stable in 5% dextrose injection for up to 15 days at room temperature and at least 120 days at 5 degrees C. Unbuffered mitomycin admixtures should not be stored or administered by prolonged i.v. infusion.     

Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature

The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high-performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen.     

Stability of ceftazidime and amino acids in parenteral nutrient solutions

The stability of ceftazidime was studied under conditions simulating administration via a Y-injection site into a primary infusion of parenteral nutrient (PN) solution; the stabilities of ceftazidime and amino acids when the drug was added directly to PN solutions were also studied. Three PN solutions containing 25% dextrose were used; the amino acid contents were 0, 2.5%, and 5%. Ceftazidime with sodium carbonate was used to prepare stock solutions of ceftazidime 40 mg/mL in both 0.9% sodium chloride injection and 5% dextrose injection; to simulate Y-site injection, samples were added to the three PN solutions to achieve ceftazidime concentrations of 10 and 20 mg/mL, or 1:1 and 1:3 ratios of drug solution to PN solution. Samples of these admixtures were assayed by high-performance liquid chromatography (HPLC) initially and after room-temperature (22 degrees C) storage for one and two hours. Additional solutions were prepared by adding sterile water for injection to ceftazidime with sodium carbonate; drug solutions were added to each PN solution in polyvinyl chloride bags to achieve ceftazidime concentrations of 1 and 6 mg/mL. The samples were assayed by HPLC for ceftazidime concentration after storage at 22 degrees C for 3, 6, 12, 24, and 36 hours and at 4 degrees C for 1, 3, 7, and 14 days. Amino acid stability was analyzed in admixtures containing 5% amino acids and ceftazidime 6 mg/mL after 24 and 48 hours at 22 degrees C and after 7 and 10 days at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activity of antibiotic admixtures subjected to different freeze-thaw treatments

The freezing of antibiotic admixtures has been proposed as a potentially useful method by which the efficiency of admixture services might be improved. The time involved in thawing, however, has discouraged the implementation of this practice. This study describes a technique of thawing frozen antibiotic admixtures contained in minibags in commercially available microwave ovens. A quantitative microbiological agar gel diffusion assay was employed to determine the effect of such treatment on the antibiotic activity of the admixture. Admixtures containing cephalothin sodium, cefazolin sodium, cefamandole nafate, cefoxitin sodium, penicillin G potassium, ampicillin sodium, oxacillin sodium, carbenicillin disodium, and gentamicin sulfate in dextrose 5% solution were frozen at -20 degrees C for 30 days. The admixtures were assayed immediately before freezing, and again after either thawing technique: that is, upon exposure of the minibags to room temperature air or to microwave radiation. Assays were also performed 8 and 24 hours after thawing in order to assess antibiotic stability following each freeze-thaw treatment. It was discovered that, with the exception of ampicillin sodium, each of the antibiotics studied could be frozen and thawed as described without significant loss of activity, and were stable for 24 hours after thawing. The application of a freeze microwave-thaw technique to central admixture services can be seen as a cost-effective method of circumventing many of the problems associated with existing programs.     

Physical and chemical stability of etoposide phosphate solutions

OBJECTIVE: To evaluate the physical and chemical stability of etoposide phosphate solutions over 7 days at 32 degrees C and 31 days at 4 degrees C and 23 degrees C: (1) at etoposide concentrations of 0.1 and 10 mg/mL as phosphate in 0.9% sodium chloride injection and 5% dextrose injection and (2) at etoposide concentrations of 10 and 20 mg/mL as phosphate in bacteriostatic water for injection packaged in plastic syringes. DESIGN: Test samples of etoposide phosphate were prepared in polyvinyl chloride (PVC) bags of the two infusion solutions at etoposide concentrations of 0.1 and 10 mg/mL as phosphate. Additional test samples were prepared in bacteriostatic water for injection containing benzyl alcohol 0.9% at etoposide concentrations of 10 and 20 mg/mL as phosphate and were packaged in 5 mL plastic syringes. Evaluations for physical and chemical stability were performed initially; after 1 and 7 days of storage at 32 degrees C; and after 1, 7, 14, and 31 days of storage at 4 degrees C and 23 degrees C. Physical stability was assessed using visual observation in normal light and using a high-intensity monodirectional light beam. Turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic (HPLC) analytic technique. RESULTS: All samples were physically stable throughout the study. Little or no change in particulate burden and haze level were found. In the intravenous infusion solutions, little or no loss of etoposide phosphate occurred in any of the samples throughout the study period. The 10 and 20 mg/mL samples in bacteriostatic water for injection repackaged in syringes were also stable throughout the study, exhibiting a maximum of 6% or 7% loss after 31 days of storage at 23 degrees C and less than 4% in 31 days at 4 degrees C. CONCLUSION: Etoposide phosphate prepared as intravenous admixtures of etoposide 0.1 and 10 mg/mL as phosphate in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as etoposide 10 and 20 mg/mL as phosphate in bacteriostatic water for injection packaged in plastic syringes is physically and chemically stable for at least 7 days at 32 degrees C and 31 days at 4 degrees C and 23 degrees C. This new water-soluble phosphate-ester of etoposide formulation solves the precipitation problems associated with the old organic solvent and surfactant-based formulation.     

Stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in portable pump reservoirs

The stability of cefazolin sodium, cefoxitin sodium, ceftazidime, and penicillin G sodium in prefilled drug reservoirs that were stored at -20 degrees C for 30 days, thawed at 5 degrees C for four days, and pumped at 37 degrees C for one day was studied. Each antimicrobial agent was diluted with sterile water for injection to a concentration representative of the most common dosage when administered via a portable infusion pump. Ten milliliters of each drug solution was placed in individual glass vials to serve as controls, and volumes appropriate to deliver the designated dosages were loaded into the drug reservoirs. Triplicate reservoirs were prepared for each drug. One-milliliter samples from all containers were taken on days 0, 30, 31, 32, 33, 34, 34.5, and 35. All solutions were observed for color change and precipitation. Drug concentrations were determined using high-performance liquid chromatography. Leaching of the plasticizer diethylhexyl phthalate (DEHP) was analyzed by packed-column gas chromatography on days 0 and 35. No color change or precipitation was observed. No DEHP concentrations above 1 ppm were detected. More than 90% of the initial concentrations of each drug remained, except penicillin G sodium, which had a mean concentration of 83.9 +/- 0.5% at the end of the study. Cefazolin sodium, cefoxitin sodium, and ceftazidime in admixtures with sterile water for injection are stable under the conditions of this study. Penicillin G sodium should not be administered for more than 12 hours after such a cycle of freezing and thawing.     

Physical and chemical stability of gemcitabine hydrochloride solutions.

OBJECTIVE: To evaluate the physical and chemical stability of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) solutions in a variety of solution concentrations, packaging, and storage conditions. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test conditions included (1) reconstituted gemcitabine at a concentration of 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride or sterile water for injection in the original 200 mg and 1 gram vials; (2) reconstituted gemcitabine 38 mg/mL as the hydrochloride salt in 0.9% sodium chloride injection packaged in plastic syringes; (3) diluted gemcitabine at concentrations of 0.1 and 10 mg/mL as the hydrochloride salt in polyvinyl chloride (PVC) minibags of 0.9% sodium chloride injection and 5% dextrose injection; and (4) gemcitabine 0.1, 10, and 38 mg/mL as the hydrochloride salt in 5% dextrose in water and 0.9% sodium chloride injection as simulated ambulatory infusions at 32 degrees C. Test samples of gemcitabine hydrochloride were prepared in the concentrations, solutions, and packaging required. MAIN OUTCOME MEASURES: Physical and chemical stability based on drug concentrations initially and after 1, 3, and 7 days of storage at 32 degrees C and after 1, 7, 14, 21, and 35 days of storage at 4 degrees C and 23 degrees C. RESULTS: The reconstituted solutions at a gemcitabine concentration of 38 mg/mL as the hydrochloride salt in the original vials occasionally exhibited large crystal formation when stored at 4 degrees C for 14 days or more. These crystals did not redissolve upon warming to room temperature. All other samples were physically stable throughout the study. Little or no change in particulate burden or the presence of haze were found. Gemcitabine as the hydrochloride salt in the solutions tested was found to be chemically stable at all concentrations and temperatures tested that did not exhibit crystallization. Little or no loss of gemcitabine occurred in any of the samples throughout the entire study period. However, refrigerated vials that developed crystals also exhibited losses of 20% to 35% in gemcitabine content. Exposure to or protection from light did not alter the stability of gemcitabine as the hydrochloride salt in the solutions tested. CONCLUSION: Reconstituted gemcitabine as the hydrochloride salt in the original vials is chemically stable at room temperature for 35 days but may develop crystals when stored at 4 degrees C. The crystals do not redissolve upon warming. Gemcitabine prepared as intravenous admixtures of 0.1 and 10 mg/mL as the hydrochloride salt in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as a solution of 38 mg/mL in 0.9% sodium chloride injection packaged in plastic syringes is physically and chemically stable for at least 35 days at 4 degrees C and 23 degrees C. Gemcitabine as the hydrochloride salt is stable for at least 7 days at concentrations of 0.1, 10, and 38 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection stored at 32 degrees C during simulated ambulatory infusion.     

三种头孢类药物的输液稳定性影响因素研究

目的研究头孢呋辛钠、头孢曲松钠、头孢他啶三种头孢类药物的输液在5％葡萄糖注射液和0．9％氯化钠注射液中稳定性影响因素。方法在不同光照、不同温度以及不同时间条件下测定三种头孢类药物输液中药物的含量、pH值及不溶性微粒等。结果在不同光照和温度条件下,三种药物与两种输液配伍后3个小时以内含量基本稳定,头孢呋辛钠和头孢曲松钠在输液中的有关物质随着放置时间延长明显增加,头孢他啶相对不明显。结论三种头孢类药物与5％葡萄糖注射液和0．9％氯化钠注射液配伍在3个小时以内可以任意选择静脉滴注时间,但最好即配即用,其中头孢呋辛钠和头孢曲松钠最好避光滴注。在配药过程中,了解药物在输液中的稳定性影响因素有利于提高药物的临床疗效,促进合理用药。     

Stability of ipratropium bromide and salbutamol nebuliser admixtures

The physicochemical stability of an admixture of ipratropium bromide and salbutamol nebuliser solutions, 1:1 v/v, was determined by storing solutions for five days in a refrigerator at 4C, at 22C protected from light and at 22C under 24 hour fluorescent lighting. Concentrations of ipratropium and salbutamol were periodically determined using a high performance liquid chromatography assay. The nebuliser solution admixtures retained greater than 90 per cent of their original concentrations of ipratropium and salbutamol for the duration of the study. Differences in losses between storage conditions were not statistically significant. Admixtures of proprietary ipratropium bromide and salbutamol nebuliser solutions (1:1 v/v) retain greater than 90 per cent of their initial concentrations if stored between 4C and 22C for periods of up to five days. An expiry period of five days for these admixtures would seem reasonable in practice.     

Compatibility of cisplatin and fluorouracil in 0.9% sodium chloride injection

The effect of drug concentration and light on the compatibility and stability of cisplatin and fluorouracil in i.v. admixtures was studied. Two sets of admixtures were prepared in 0.9% sodium chloride injection in polyvinyl chloride bags--(1) cisplatin 200 micrograms/mL and fluorouracil 1,000 micrograms/mL and (2) cisplatin 500 micrograms/mL and fluorouracil 10,000 micrograms/mL. Half of the admixtures were protected from light. All admixtures were stored at room temperature (24-26 degrees C), and those admixtures not protected from light were stored under room fluorescent light. After visual inspection, the pH of each admixture was determined, and an aliquot was assayed for drug concentration using a stability-indicating high-performance liquid chromatographic assay. Over a four-hour period, no visual changes were observed and the pH changes observed were negligible. In admixtures containing the lower concentrations of cisplatin and fluorouracil, it took approximately 1.5 hours for the concentration of cisplatin to reach 90% of the initial concentration. By four hours (lower concentration range) and three hours (higher concentration range) after the admixtures were prepared, less than 75% of the initial cisplatin concentration remained. There was less than a 5% decrease measured in the fluorouracil concentrations over the observation time. Admixtures of cisplatin and fluorouracil in 0.9% sodium chloride injection at the concentrations evaluated in this study must be used within one hour of preparation, whether or not they are protected from light. Intravenous administration of fluorouracil and cisplatin by continuous infusion will require alternative approaches to mixing the two drugs in the same container.     

In vitro inactivation of tobramycin by cephalosporins

The in vitro inactivation of tobramycin when combined with each of six cephalosporins in samples of human serum was investigated. Each of six cephalosporins (cefazolin sodium, cefoxitin sodium, cefamandole nafate, moxalactam disodium, cefoperazone sodium, and cefotaxime sodium) was added to human serum samples containing tobramycin sulfate 8 micrograms/mL to produce final cephalosporin concentrations of approximately 250 and 1000 micrograms/mL. Duplicate solutions were prepared and stored at either 0 or 21 degrees C. Solutions containing tobramycin 8 micrograms/mL alone and with carbenicillin disodium in four concentrations were prepared as controls. Samples were assayed using a fluorescence polarization immunoassay (TDX) at 0, 2, 4, 8, 12, 24, and 48 hours to determine tobramycin concentration; two of the carbenicillin-tobramycin solutions were frozen immediately for assay 53 hours later. Tobramycin concentrations in the admixtures were compared with those in tobramycin reference samples. At both temperatures, samples containing tobramycin with cefamandole 250 micrograms/mL or cefotaxime 250 micrograms/mL showed less than 10% inactivation of tobramycin for at least 48 hours. At 0 degrees C, tobramycin retained greater than 90% activity when combined with cefoperazone 250 and 1000 micrograms/mL. In samples containing cefazolin 250 micrograms/mL at 0 degrees C and cefoperazone 250 micrograms/mL at 21 degrees C, tobramycin was stable for 24 hours. Only samples containing moxalactam stored at 21 degrees C showed greater than 16% inactivation of tobramycin at 48 hours. Under these study conditions, tobramycin is only moderately inactivated in vitro when combined with clinically achievable concentrations of the tested cephalosporins (excluding moxalactam) and then stored for up to 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)